Mortality in Friedreich Ataxia

Tsou, Amy Y.; Paulsen, Erin K.; Lagedrost, Sarah J.; Perlman, Susan; Mathews, Katherine D.; Wilmot, George; Ravina, Bernard; Koeppen, Arnulf H.; Lynch, David R.

doi:10.1016/j.jns.2011.05.023

Cited by 253 publications

(242 citation statements)

References 11 publications

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“…1,5,11 Cardiac involvement determines survival prospects. 1,4,12 Identifying early markers of cardiac involvement should enable the more aggressive institution of cardioprotective therapies to delay disease progression, although effective treatments remain in development. 5 Our group has previously shown that myocardial fibrosis can occur in FA patients who do not have overt cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 The left ventricle (LV) in patients with FA cardiomyopathy might exhibit hypertrophy, dilation, or concentric remodeling; arrhythmias and heart failure contribute to death. 1,4,5 Cardiac magnetic resonance (CMR) affords direct, in vivo evaluation of LV remodeling and fibrosis that can develop before cardiomyopathy in FA becomes clinically apparent. 6 The myocardial extracellular matrix plays a key role in determining myocardial architecture.…”

Section: Serum Versus Imaging Biomarkers In Friedreich Ataxiamentioning

confidence: 99%

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Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes

Mehta¹,

Chacko²,

Jin³

et al. 2016

Texas Heart Institute Journal

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Patients with Friedreich ataxia typically die of cardiomyopathy, marked by myocardial fibrosis and abnormal left ventricular (LV) geometry. We measured procollagen I carboxyterminal propeptide (PICP), a serum biomarker of collagen production, and characterized genotypes, phenotypes, and outcomes in these patients. Twenty-nine patients with Friedreich ataxia (mean age, 34.2 ± 2.2 yr) and 29 healthy subjects (mean age, 32.5 ± 1.1 yr) underwent serum PICP measurements. Patients underwent cardiac magnetic resonance imaging and outcome evaluations at baseline and 12 months. Baseline PICP values were significantly higher in the patients than in the control group (1,048 ± 77 vs 614 ± 23 ng/mL; P <0.001); severity of genetic abnormality did not indicate severity of PICP elevation. Higher PICP levels corresponded to greater LV concentric remodeling only at baseline (r=0.37, P <0.05). Higher baseline PICP strongly indicated subsequent increases in LV end-diastolic volume (r=0.52, P=0.02). The PICP levels did not distinguish between 14 patients with evident myocardial fibrosis identified through positive late gadolinium enhancement and 15 who had no enhancement (1,067 ± 125 vs 1,030 ± 98 ng/mL; P=0.82). At 12 months, cardiac events had occurred in 3 of 14 fibrosis-positive and none of 15 fibrosis-negative patients (P=0.1); their baseline PICP levels were similar. We conclude that PICP, a serum marker of collagen synthesis, is elevated in Friedreich ataxia and indicates baseline abnormal LV geometry and subsequent dilation. Cardiac magnetic resonance and PICP warrant consideration as complementary biomarkers in therapeutic trials of Friedreich ataxia cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

Section: Serum Versus Imaging Biomarkers In Friedreich Ataxiamentioning

confidence: 99%

Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes

Mehta¹,

Chacko²,

Jin³

et al. 2016

Texas Heart Institute Journal

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“…The prognosis is associated with the number of GAA repeats. 1,3 Like what has been observed in other rare diseases, the clinical spectrum of FA has expanded considerably because family screening and genetic testing have enabled earlier diagnosis in asymptomatic or mildly symptomatic relatives.…”

Section: The Genetic Basis Of Fa: a Mitochondrial Diseasementioning

confidence: 99%

“…The mean life expectancy is significantly reduced to Ϸ40 years, and Ϸ60% of patients with FA die from cardiac causes. 1,2 The prevalence of FA is 0.1 to 4.7:100 000, and an estimated 9000 Americans are affected. 3 The potential ability to reduce disease progression or even to reverse FA-CM by antioxidants underscores the importance of early identification of the disease and the development of clinically identifiable markers of cardiac involvement.…”

mentioning

confidence: 99%

Cardiomyopathy in Friedreich Ataxia

Jensen

Bundgaard

2012

Circulation

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“…Along with the central and peripheral nervous system, heart and pancreas are also affected (Harding, 1981) in patients. Cardiac dysfunction is the predominant reason for mortality in affected individuals (Tsou et al, 2011). Approximately 10% of patients develop diabetes.…”

Section: Introductionmentioning

confidence: 99%